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Estradiol valerate with medroxyprogesterone acetate and placebo oral

Updated 2 Feb 2023 | Oestrogens and HRT


Tablets containing estradiol valerate
Tablets containing estradiol valerate with medroxyprogesterone acetate
Tablets containing a placebo

Drugs List

  • estradiol valerate 2mg tablets and estradiol valerate 2mg with medroxyprogesterone acetate 20mg tablets and placebo tablets
  • TRIDESTRA tablets
  • Therapeutic Indications


    Hormone replacement therapy for the treatment of the climacteric syndrome
    Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture



    One tablet daily for 91 days, according to the calendar pack.

    If patient is still menstruating commence treatment on day 5 of cycle.

    In women with amenorrhoea and not taking hormone replacement therapy (HRT) or women who switch from another continuous combined HRT product, treatment may be started on any day. Women who switch from cyclic HRT regimen should start treatment one week after completion of the cycle.

    Start the next pack immediately after taking the last placebo tablet.

    If patient has forgotten to take one tablet, it should be taken within 12 hours otherwise the forgotten tablet should be discarded. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.


    (See Dosage; Adults)


    Major surgery with prolonged post-operative immobilisation
    Abnormal liver function test
    Cerebrovascular accident
    Deep vein thrombosis
    Familial conjugated hyperbilirubinaemias
    Hepatic neoplasm
    History of thromboembolic disorder
    Oestrogen dependent neoplasm
    Pulmonary embolism
    Severe arterial disorder
    Thromboembolic disorder
    Uncontrolled endometrial hyperplasia
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Body mass index above 30kg per square metre
    Family history of breast cancer
    Family history of thromboembolic disorder
    History of recurrent spontaneous abortion
    Patients over 65 years
    Predisposition to thromboembolic disease
    Risk factor for oestrogen-dependent neoplasm
    Severe headache
    Breast nodules
    Cardiac impairment
    Diabetes mellitus
    Endometrial hyperplasia
    Epileptic disorder
    Fibrocystic breast disorder
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    Hereditary angioneurotic oedema
    History of breast nodules
    History of chloasma
    History of depression
    History of endometriosis
    History of fibrocystic breast disorder
    History of jaundice
    History of otosclerosis
    Hypophyseal neoplasm
    Lactose intolerance
    Malignant neoplasm
    Renal impairment
    Systemic lupus erythematosus
    Uterine fibroids

    Assess family medical history prior to commencing treatment
    Exclude oestrogen dependent neoplasm before treatment
    Pre-treatment medical history and clinical examination
    Contains lactose
    Resume use only after 2wks full ambulation from surgery/immobilisation
    Do breast & pelvic exam. before & during treatment if clinically indicated
    Abnormal and/or irregular bleeding should be investigated
    Monitor blood glucose closely in patients with diabetes mellitus
    Monitor hepatic function in patients with history of hepatic disease
    Advise patient of thromboembolic symptoms and to report them if they occur
    Advise patient that changes in their breasts should be reported to Dr/nurse
    Increased risk of VTE during travel involving >5hr immobilisation
    Combined HRT therapy may prevent radiological detection of breast cancer
    May affect results of some laboratory tests
    Discontinue 4 - 6 weeks before major surgery
    Advise patient to seek advice at first indications of pregnancy
    Discontinue at first signs of thrombophlebitis or thromboembolism
    Discontinue if cholestasis develops
    Discontinue if epilepsy is exacerbated
    Discontinue if first occurrence or worsening of migraine/severe headache
    Discontinue if first occurrence or worsening of visual disturbances
    Discontinue if headache assoc with weakness/numbness one side/part occurs
    Discontinue if headache associated with sudden dysphasia or vertigo occurs
    Discontinue if headache associated with sudden motor disturbances occurs
    Discontinue if jaundice or other evidence of hepatic impairment occurs
    Discontinue if severe pain in the calf of one leg occurs
    Discontinue if significant rise in blood pressure occurs
    Discontinue if sudden breathlessness (or cough with blood stained sputum)
    Discontinue if sudden occurrence of visual/hearing/perceptual disorders
    Discontinue if sudden pain in the chest occurs
    Discontinue if sudden, severe pain in stomach occurs
    Discontinue if symptoms due to endometriosis are exacerbated
    Advise patient not to take St John's wort concurrently
    Female: Not for contraception.Use non-hormonal contraception, if required
    Advise patient of increased risk of breast cancer vs benefits of HRT
    Women with a history of chloasma should avoid exposure to sun/UV light

    For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.

    Pregnancy and Lactation


    Hormone replacement therapy is contraindicated during pregnancy.

    Developmental changes in the psychosexual performance of boys have been attributed to in utero exposure to estradiol and progesterone. Hormone exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls. The use of estrogenic hormones during pregnancy is contraindicated.

    Medroxyprogesterone demonstrates dose-related teratogenicity and toxicity in animals. Although the hormone is contraindicated in human pregnancy, inadvertent exposure to therapeutic dose does not appear to represent a significant risk of structural defects. Foetal growth retardation might be a low risk complication if administered within 4 weeks of conception.

    The accidental administration of high-dose preparations has no risk-based reason for a termination of pregnancy. In the case of repeated high-dose administration, at least, a details ultrasound examination could verify a normal morphologic development of the foetus.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Hormone replacement therapy is contraindicated during lactation.

    There is limited information on the use of estradiol during breastfeeding but is capable of transfer into breast milk. The amount of milk produced can decrease as a result of the influence of estrogens.

    Medroxyprogesterone studies indicate that concerns about immediate adverse effects on the infant is unfounded, however there is no data on the effects of progesterone on brain and liver development at this age. There is little or no effect on the milk supply and only a very limited effect on the composition.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at


    Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age. Breast awareness should also be encouraged and patients advised to report any changes in their breasts to their doctor or nurse

    Advise patients to contact their doctor if they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

    If patient has forgotten to take one tablet, the forgotten tablet should be taken within 12 hours or otherwise discarded. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

    Advise patient to seek advice at the first indications of pregnancy.

    Advise patient of increased risk of breast cancer versus the benefits of HRT.

    Side Effects

    "Spotting" bleeding
    Abdominal cramps
    Aggravation of porphyria
    Allergic skin reactions
    Altered glucose tolerance
    Breakthrough bleeding
    Breast enlargement
    Breast tenderness
    Changes in libido
    Cholestatic jaundice
    Endometrial hyperplasia
    Erythema multiforme
    Erythema nodosum
    Exacerbation of angioedema
    Fluid retention
    Gallbladder disease
    Increase in plasma triglyceride concentration
    Increased risk of breast cancer
    Increased risk of endometrial cancer
    Increased size of uterine fibroids
    Intolerance to contact lenses
    Ischaemic stroke
    Leg cramps
    Mood changes
    Myocardial infarction
    Premenstrual-like syndrome
    Sodium retention
    Visual disturbances
    Weight changes

    Effects on Laboratory Tests

    The use of oestrogen-progestogen combinations may affect clinical laboratory results. There may be an increase in serum transaminases, alkaline phosphatase, gamma-glutamyltransferase, bilirubin and binding proteins. Thyroid-binding globulin may rise leading to erroneous results in thyroid function tests.

    HRT, especially oestrogen - progestogen combined therapy, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: December 2015

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

    Summary of Product Characteristics: Tridestra. Orion Pharma (UK) Limited. Revised November 2021.

    The Norwegian Porphyria Centre (NAPOS).
    Available at:
    Last accessed: 02 December 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Estradiol. Last revised: 02 June 2015
    Last accessed: 02 December 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Medroxyprogesterone. Last revised: 01 October 2015
    Last accessed: 02 December 2015

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